title: Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206.
abstract: OBJECTIVE
  Bevacizumab is an antibody that binds to vascular endothelial growth factor (VEGF) and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN) is a historic standard first-line treatment for RCC. A prospective, randomized phase III trial of bevacizumab plus IFN versus IFN monotherapy was conducted.
  
  
  METHODS
  Patients with previously untreated, metastatic clear-cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN (9 million U subcutaneously three times weekly) or the same dose and schedule of IFN monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety.
  
  
  RESULTS
  Between October 2003 and July 2005, 732 patients were enrolled. The prespecified stopping rule for OS has not yet been reached. The median PFS was 8.5 months in patients receiving bevacizumab plus IFN (95% CI, 7.5 to 9.7 months) versus 5.2 months (95% CI, 3.1 to 5.6 months) in patients receiving IFN monotherapy (log-rank P < .0001). The adjusted hazard ratio was 0.71 (95% CI, 0.61 to 0.83; P < .0001). Bevacizumab plus IFN had a higher ORR as compared with IFN (25.5% [95% CI, 20.9% to 30.6%] v 13.1% [95% CI, 9.5% to 17.3%]; P < .0001). Overall toxicity was greater for bevacizumab plus IFN, including significantly more grade 3 hypertension (9% v 0%), anorexia (17% v 8%), fatigue (35% v 28%), and proteinuria (13% v 0%).
  
  
  CONCLUSIONS
  Bevacizumab plus IFN produces a superior PFS and ORR in untreated patients with metastatic RCC as compared with IFN monotherapy. Toxicity is greater in the combination therapy arm.
authors.affiliation: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA. rinib2@ccf.org
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Vaena
authors.forename: San-San
authors.initials: SS
authors.lastname: Ou
authors.forename: Laura
authors.initials: L
authors.lastname: Archer
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Piotr
authors.initials: P
authors.lastname: Czaykowski
authors.forename: Janice
authors.initials: J
authors.lastname: Dutcher
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016898:Interferon-alpha; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab